Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice

Francisco J Urbano; Noelia G Lino; Carlota M. F González-Inchauspe; Laura E González; Natalia Colettis; Lucas G Vattino; Amanda M Wunsch; John A Wemmie; Osvaldo D Uchitel

doi:10.1152/ajpcell.00301.2013

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Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice

Journal article

Peer reviewed

Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice

Francisco J Urbano, Noelia G Lino, Carlota M. F González-Inchauspe, Laura E González, Natalia Colettis, Lucas G Vattino, Amanda M Wunsch, John A Wemmie and Osvaldo D Uchitel

American Journal of Physiology: Cell Physiology, Vol.306(4), pp.C396-C406

02/15/2014

DOI: 10.1152/ajpcell.00301.2013

PMCID: PMC3919981

PMID: 24336653

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Abstract

Acid-sensing ion channels (ASIC) open in response to extracellular acidosis. ASIC1a, a particular subtype of these channels, has been described to have a postsynaptic distribution in the brain, being involved not only in ischemia and epilepsy, but also in fear and psychiatric pathologies. High-frequency stimulation of skeletal motor nerve terminals (MNTs) can induce presynaptic pH changes in combination with an acidification of the synaptic cleft, known to contribute to muscle fatigue. Here, we studied the role of ASIC1a channels on neuromuscular transmission. We combined a behavioral wire hanging test with electrophysiology, pharmacological, and immunofluorescence techniques to compare wild-type and ASIC1a lacking mice (ASIC1a\n−/−\nknockout). Our results showed that\n1\n) ASIC1a\n−/−\nfemale mice were weaker than wild type, presenting shorter times during the wire hanging test;\n2\n)\ns\npontaneous neurotransmitter release was reduced by ASIC1a activation, suggesting a presynaptic location of these channels at individual MNTs;\n3\n) ASIC1a-mediated effects were emulated by extracellular local application of acid saline solutions (pH = 6.0; HEPES/MES-based solution); and\n4\n) immunofluorescence techniques revealed the presence of ASIC1a antigens on MNTs. These results suggest that ASIC1a channels might be involved in controlling neuromuscular transmission, muscle contraction and fatigue in female mice.

wire hanging

extracellular acidosis

presynaptic modulation

acid-sensing ion channels

motor nerve transmission

Details

Title: Subtitle: Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice
Creators: Francisco J Urbano - Laboratorio de Fisiología y Biología Molecular (LFBM), Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires, Argentina; and
Noelia G Lino - Laboratorio de Fisiología y Biología Molecular (LFBM), Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires, Argentina; and
Carlota M. F González-Inchauspe - Laboratorio de Fisiología y Biología Molecular (LFBM), Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires, Argentina; and
Laura E González - Laboratorio de Fisiología y Biología Molecular (LFBM), Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires, Argentina; and
Natalia Colettis - Laboratorio de Fisiología y Biología Molecular (LFBM), Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires, Argentina; and
Lucas G Vattino - Laboratorio de Fisiología y Biología Molecular (LFBM), Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires, Argentina; and
Amanda M Wunsch - Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa
John A Wemmie - Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa
Osvaldo D Uchitel - Laboratorio de Fisiología y Biología Molecular (LFBM), Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Intendente Güiraldes 2160, Ciudad Universitaria, Buenos Aires, Argentina; and
Resource Type: Journal article
Publication Details: American Journal of Physiology: Cell Physiology, Vol.306(4), pp.C396-C406
DOI: 10.1152/ajpcell.00301.2013
PMID: 24336653
PMCID: PMC3919981
NLM abbreviation: Am J Physiol Cell Physiol
ISSN: 0363-6143
eISSN: 1522-1563
Publisher: American Physiological Society; Bethesda, MD
Language: English
Date published: 02/15/2014
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984066378802771

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